HLA-G mediated immune regulation is impaired by a single amino acid exchange in the alpha 2 domain
HLA-G mediated immune regulation is impaired by a single amino acid exchange in the alpha 2 domain
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DOI：
10.1016/j.humimm.2018.03.010
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发表时间：
2018-06-01
期刊：
影响因子：
2.7
通讯作者：
Bade-Doeding, Christina
中科院分区：
文献类型：
--
作者：
Celik, Alexander A.;Simper, Gwendolin S.;Bade-Doeding, Christina
从HLA I类表达到HLA- g表达的权衡支持恶性细胞的免疫逃避。几乎不变的HLA-G在免疫耐受、肿瘤免疫学中的重要作用及其在免疫特权组织中的表达频率是已知的；然而，等位基因亚型在免疫反应中的具体重要性仍未得到很好的理解。HLA-G*01:01， *01:03和*01:04是最普遍的等位变异，分别在残基31和110处不同。在以HLA-G变异体转导的K562细胞为靶点，NK细胞为效应器的细胞毒性实验中，分析了HLA-G变异体的不同保护潜力。利用可溶性HLA技术测定其肽谱。可以观察到HLA-G*01:04的保护潜力增加。所有变异都表现出独特的肽库，并有边缘重叠，而G*01:04在肽锚谱上有很大的不同。HLA-G亚型之间的功能差异可以通过结合肽的限制来解释，改变了pHLA-G的可及表面。首次可以观察到HLA-G重链内的氨基酸改变对肽选择和NK细胞识别的贡献。这些结果将是了解免疫耐受的一步，并将指导个性化的免疫治疗策略。
The trade-off from HLA class I expression to HLA-G expression support the immune evasion of malignant cells. The essential role of the virtually invariant HLA-G in immune tolerance, tumor immunology and its expression frequency in immune privileged tissues is known; however the specific importance of allelic subtypes in immune responses is still not well understood. HLA-G*01:01, *01:03 and *01:04 are the most prevalent allelic variants differing at residues 31 and 110, respectively. In cytotoxicity assays applying K562 cells transduced with the HLA-G variants as targets and NK cells as effectors the differential protective potential of HLA-G variants was analyzed. Their peptide profiles were determined utilizing soluble HLA technology. An increased protective potential of HLA-G*01:04 could be observed. All variants exhibit a unique peptide repertoire with marginal overlap, while G*01:04 differs in its peptide anchor profile substantially. The functional differences between HLA-G subtypes could be explained by the constraint of the bound peptides, modifying the pHLA-G accessible surface. For the first time a contribution of amino acid alterations within the HLA-G heavy chain for peptide selection and NK cell recognition could be observed. These results will be a step towards understanding immune tolerance and will guide towards personalized immune therapeutic strategies.